Data_Sheet_1_Structural and Diffusion MRI Analyses With Histological Observations in Patients With Lissencephaly.docx

The development of cortical convolutions, gyri and sulci, is a complex process that takes place during prenatal development. Lissencephaly, a rare genetic condition characterized by the lack of cortical convolutions, offers a model to look into biological processes that lead to the development of convolutions. Retrospective, qualitative, and quantitative analyses of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed in patients with lissencephaly (N = 10) and age-/sex-matched controls (N = 10). In order to identify microstructural correlates of structural MRI and DTI findings, postmortem brains of patients with lissencephaly (N = 4) and age-matched controls (N = 4) were also examined with histology. Patients with lissencephaly had significantly smaller gyrification index and volumes of hemispheric white and gray matter, compared to the age-/sex-matched control group. However, there was no significant difference between groups in the subcortical gray matter volumes. Although the majority of patients with lissencephaly had a preserved normal-like appearance of major fissures and primary sulci, the spatial distribution of agyric cortical regions was different in patients with lissencephaly-1 (LIS1) and doublecortin (DCX) mutations. Lastly, in patients with lissencephaly, the spatiotemporal distribution of projection pathways was preserved while short- to medium-range cortico-cortical pathways were absent or fewer in number. Our results indicate that in the patients with lissencephaly cortical system is affected more than the subcortical one.

皮质折叠、脑回和脑沟的形成是发生在孕期发育过程中的一个复杂过程。无脑回畸形，一种以皮质折叠缺失为特征的罕见遗传性疾病，为研究导致折叠形成的生物学过程提供了一个模型。对10名无脑回畸形患者及年龄和性别相匹配的对照组（均为10名）的结构磁共振成像（MRI）和弥散张量成像（DTI）进行了回顾性、定性和定量分析。为了识别结构MRI和DTI发现的结构微结构相关性，还使用组织学对4名无脑回畸形患者和4名年龄相匹配的对照组的脑部进行了尸检。与年龄和性别相匹配的对照组相比，无脑回畸形患者的脑回指数和半球白质、灰质的体积显著较小。然而，两组在皮质下灰质体积方面没有显著差异。尽管大多数无脑回畸形患者的主要裂隙和初级脑沟的形态与正常相似，但无脑回畸形-1（LIS1）和双皮质素（DCX）突变患者的无脑回皮质区域的空間分布不同。最后，在无脑回畸形患者中，投射通路的空间时间分布得以保留，而短至中距离的皮质-皮质通路则缺失或数量较少。我们的结果表明，在无脑回畸形患者中，皮质系统受影响的程度超过皮质下系统。